1. Related F-box proteins control cell death in Caenorhabditis elegans and human lymphoma.
- Author
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Chiorazzi, Michael, Rui, Lixin, Yandan Yang, Ceribelli, Michele, Tishbi, Nima, Maurer, Carine W., Ranuncolo, Stella M., Hong Zhao, Weihong Xu, Chan, Wing-Chung C., Jaffe, Elaine S., Gascoyne, Randy D., Campo, Elias, Rosenwald, Andreas, Otth, German, Delabie, Jan, Rimsza, Lisa M., Shaham, Shai, and Staudt, Louis M.
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CELL death ,CAENORHABDITIS elegans ,LYMPHOMAS ,CASPASES ,APOPTOSIS ,PREVENTION - Abstract
Cell death is a common metazoan cell fate, and its inactivation is central to human malignancy. In Caenorhabditis elegans, apoptotic cell death occurs via the activation of the caspase CED-3 following binding of the EGL-1/BH3-only protein to the antiapoptotic CED-9/ BCL2 protein. Here we report a major alternative mechanism for caspase activation in vivo involving the F-box protein DRE-1. DRE-1 functions in parallel to EGL-1, requires CED-9 for activity, and binds to CED-9, suggesting that DRE-1 promotes apoptosis by inactivating CED-9. FBXO10. a human protein related to DRE-1, binds BCL2 and promotes its degradation, thereby initiating cell death. Moreover, some human diffuse large B-cell lymphomas have inactivating muta- tions in FBXO10 or express FBXO10 at low levels. Our results suggest that DRE-1/FBXO10 is a conserved regulator of apoptosis. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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